Hypomagnesemia and Prognosis in Newly Diagnosed Diffuse Large B Cell Lymphoma

Magnesium (Mg) is an essential element that is involved in cellular metabolism. Hypomagnesemia occurs due to inadequate diet and urinary losses which can be induced by platinum-based chemotherapy. We previously demonstrated that low serum Mg (<1.7 mg/dL) occurred in 14% of patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplant and was associated with increased non-relapse mortality. In this study we investigated whether the pre-treatment serum Mg levels in patients with DLBCL are predictive of event-free survival (EFS) and overall survival (OS). We obtained frozen pretreatment serum from 408 patients using the resources of the Iowa/Mayo Lymphoma SPORE Biospecimens Core and analyzed the serum Mg level (normal range, 1.7-2.3 mg/dL) in the Mayo Clinic Core Laboratory. Fourteen patients (4%) had low serum Mg (<1.7 mg/dL) and 95 (23%) had serum Mg levels <2.0 mg/dL. Low/low normal (<2.0 mg/dL) levels were associated with higher stage at diagnosis (p = 0.027), more extranodal involvement (p < 0.001), higher lymphoma international prognostic index (IPI) score (p = 0.006), and shorter OS (HR, 1.4; 95% CI, 0.97-2.03, p = 0.07) and EFS (HR, 1.33; 95% CI, 0.95-1.87, p = 0.09) compared to those with serum Mg levels (≥2.0 mg/mL). In a multivariate analysis of EFS/OS, the low serum Mg was not independent of the IPI.

Conclusions: Hypomagnesemia is uncommon in DLBCL patients prior to treatment but is associated with high-risk disease. Since low Mg is one of few actionable prognostic factors, we recommend that nutritional counseling be included in the pretreatment evaluation of these patients. The feasibility and efficacy of replacing Mg to normal levels in lymphoma patients is the focus of our ongoing trial (NCT05294367).

Panel A: Overall survival of patients with diffuse large B-cell lymphoma by pre-therapy serum magnesium levels.

Panel B: Event free survival of patients with diffuse large B-cell lymphoma by pre-therapy serum magnesium levels.

Maurer:Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; GenMab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Roche/Genentech: Research Funding. Witzig:Kura Oncology: Other: Clinical Trail Support; Curio Science: Honoraria; Karyopharm: Other: Clinical Trail Support; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees.